The general hypothesis is that pharmacological manipulation of the cellular immune response may be a successful anticancer therapeutic strategy. Preliminary data suggest that the therapeutic combination of bryostatin I (bryo) and interleukin-2 (IL-2) in an appropriate schedule and dose may be superior to either agent alone and represent an effective therapy. The primary mechanistic hypothesis is that pharmacological activation of T cells by bryostatin can enhance T cell-related therapeutic effects of IL-2. Preliminary data suggest that the dose response relationship for bryostatin modulation of IL-2-related therapeutic effects is biphasic such that optimal bryostatin doses are substantially less than maximum tolerated bryostatin doses. The applicants also propose a clinical phase Ia/Ib trial to identify, on the basis of intermediate markers of immune activation, a bryostatin+IL-2 dose combination appropriate for phase II investigation. Bryostatin is being developed by CTEP, NCI. The applicants have an approved Letter of Intent for this study, and comments upon a draft protocol have been received. These are discussed under Research Design and Methods. Presuming successful completion of this study, future directions would include (1) phase II trials of bryostatin+IL-2 in renal cell carcinoma and melanoma, and (2) further development of pharmacological immunotherapy through the addition of other immune active agents to the bryostatin+IL-2 combination.